Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Curr Genomics. 2009 Jun;10(4):231-9. doi: 10.2174/138920209788488526.
Malignant melanoma represents one of the most aggressive malignancies but outcome is highly variable with early tumor lesions having an excellent prognosis following resection. We review here the data on identification of genes involved in the progression of melanoma as a result of expression array studies, genomic profiling, and genetic models. We focus on the role of tumor suppressors involved in cell cycle function, DNA repair, and genome maintenance. Highlighted are the roles of loss of p16 in promoting neoplasia in cooperation with deregulated MAPK signaling, and the role of loss of the RASSF1A protein in promoting chromosomal instability. The interactions between point mutation in growth signaling molecules and epigenetic changes in genes involved in DNA repair and cell division are discussed.
恶性黑色素瘤是最具侵袭性的恶性肿瘤之一,但由于早期肿瘤病变切除后预后良好,其结局具有高度可变性。在此,我们回顾了由于表达谱研究、基因组分析和遗传模型而鉴定出参与黑色素瘤进展的基因的数据。我们重点关注参与细胞周期功能、DNA 修复和基因组维护的肿瘤抑制因子的作用。强调了 p16 缺失在与失调的 MAPK 信号协同促进肿瘤发生中的作用,以及 RASSF1A 蛋白缺失在促进染色体不稳定性中的作用。讨论了生长信号分子点突变与涉及 DNA 修复和细胞分裂的基因中的表观遗传变化之间的相互作用。